Inflammation caused by inflammatory reaction

Pathology

1. INFLAMMATION
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2. OBJECTIVES
•Be able to define Inflammation
•Know the cardinal signs of inflammation
•Understand the process/steps of inflammations
•Comprehend the etiopathogenesis of granulomatous
inflammations
•Contrast the differences between acute and chronic
inflammations
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3. •Is “A dynamic response of vascularised tissue to injury.”
•A reaction of a living tissue & its micro-circulation to a
pathogenic insult.
•A protective response intended to eliminate the initial
cause of cell injury as well as the necrotic cells and tissues
resulting from the original insult.
•It serves to bring defense & healing mechanisms to the site
of injury.
What is Inflammation?
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4. Inflammation cont…
The main components of inflammation are:
1.Vascular reaction
2.Cellular response;
•Both are activated by mediators that are derived from
plasma proteins and various cells (IL-1, cytokines..).
•Although inflammation helps clear infections and other
noxious stimuli and initiates repair, the inflammatory
reaction and the subsequent repair process can cause
considerable harm.
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5. •The can be remembered as -five R’s:
1.Recognitionoftheinjuriousagent
2.Recruitmentofleukocytes,
3.Removaloftheagent,
4.Regulation(control)oftheresponse,and
5.Resolution(repair)..
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Steps of the inflammatory response

6. Nomenclature
•The nomenclatures of inflammatory lesion are indicated by
the suffix 'itis‘ commonly.
Examples : -Appendicitis
-Cellulitis
-Meningitis
-Nephritis
-Myocarditis
•However, like any rule, it has its own exceptions.
Examples: -pneumonia,
-typhoid fever,
-rheumatic fever etc. 6

7. Etiologies of Inflammation
•Infectious agents--bacteria, viruses, parasites, fungi, etc.
•Physical agents: burns, trauma (cuts), radiation
•Chemicals: toxins and caustic substances like battery acid
•Immunologic reactions--Asthma, Rheumatoid Arthritis
•Genetic/metabolic disorders-examples gout, diabetes
mellitus etc…
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8. Classification
1.Acute inflammation-
–is of relatively short duration
–lasting from a few minutes up to a few days,
–is characterized by fluid and plasma protein exudation and a
predominantly neutrophilicleukocyte accumulation.
2.Chronic Inflammation-
–is of longer duration (days to years)
–Has predominantly lymphocytes and macrophages with
associated vascular proliferation and scarring
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9. Acute inflammation
Chronic inflammation
RepairResolution
Abscess
Injury
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10. ACUTE INFLAMMATION
•Is an immediate and early response to an injurious agent
and it is relatively of short duration, lasting for minutes,
several hours or few days.
•It is characterized by exudation of fluids and plasma
proteins and the emigration of predominantly neutrophilic
leucocytes to the site of injury.
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11. ACUTE INFLAMMATION CONT…
•There arefive cardinal signs of acute inflammation :
1-Redness (rubor) -is due to dilation of small blood
vessels within damagedtissue.
2-Heat (calor)-results from increased blood flow
(hyperemia) due to regional vascular dilation
3-Swelling (tumor) -is due to accumulation of fluid in
the extravascular space which, in turn, is due to
increased vascular permeability.
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12. 4-Pain (dolor)-partly results from the stretching &
destruction of tissues due to inflammatory edema and in
part from pus under pressure as in abscess cavity.
-Some chemicals of acute inflammation, including
bradykinins, prostaglandins and serotonin are also
known to induce pain.
5-Loss of function:
The inflamed area is inhibited by pain while severe
swelling may also physically immobilize the tissue.
ACUTE INFLAMMATION CONT…
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13. 13

14. 1.Vascular changes –first three of the cardinal signs
Stages:
a) Immediate(momentary) vasoconstrictionin seconds due
to neurogenic or chemical stimuli.
b) Vasodilatationof arterioles and venulesresulting in
increased blood flow.
c) Slowing of blood flow( stasis) due to increased vascular
permeability that is most remarkably seen in the post-
capillary venules.
Events of acute inflammation
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15. •The increased vascular permeability oozes protein-rich
fluid into extra vascular tissues.
•Lymphatics are responsible for draining edema.
•Edema: An excess of fluid in the interstitial tissue or
serous cavities; either atransudateor an exudate
Transudate:
–An ultra filtrate of blood plasma
–permeability of endothelium is usually normal
–low protein content ( mostly albumin)
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16. Exudate:
•A filtrate of blood plasma mixed with inflammatory
cells and cellular debris.
–permeability of endothelium is usually altered
–high protein content.
Pus: A purulent exudate: an inflammatory exudate
rich in leukocytes (mostly neutrophils) and
parenchymalcell debris.
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17. 17

18. 2. Cellular response (Activation & recruitment of lekocytes)
•Next two of the cardinal signs of inflammation
•The cellular response has the following stages:
A. Margination, rolling, pavementing, & adhesion of leukocytes
B. Transmigration of leukocytes
C. Chemotaxis
D. Phagocytosis
•Normally blood cells particularly erythrocytes in venules are
confined to the central(axial) zone and plasma assumes the
peripheral zone.
•increased vascular permeability causes more and more neutrophils to
accumulate along the endothelial surfaces (peripheral zone).
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20. ➢Phagocytosis
•is the process of engulfment and internalization of
invading microorganisms, damaged cells, and tissue
debris by specialized cells.
•These phagocyticcells include: polymorphonuclear
leukocytes, monocytesand tissue macrophages.
•Phagocytosisinvolves three distinct but interrelated steps:
–1.Recognition and attachment
–2.Engulfement
–3.Degradation or killing
.
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22. Morphology of acute inflammation
•Characteristically, the acute inflammatory response
involves production of exudates.
•An exudate is an edema fluid with high protein
concentration, which frequently contains inflammatory
cells.
•A transudate is simply a non-inflammatory edema caused
by cardiac, renal, undernutritional, & other disorders.
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23. Exudate Vs Transudate
Exudative Transudative
Cause acute inflammation non inflammatory
appearance colored, turbid, Hemorrhagicclear, translucent, or pale
yellow
specific gravity>1.020 <1.020
Spontaneous
coagulability
yes no
protein content>3gm% -
Cells Abundant WBC, RBC, & cell debrisonly few mesothelialcells
Bacteria present Absent
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24. Difference between exudate and
transudate
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25. Chemical mediators of inflammation
•Chemical mediators account for the events of
inflammation.
•Inflammation has the following sequence:
•Cell injury → Chemical mediators → Acute
inflammation
•Sources of mediators:
•The chemical mediators of inflammation can be derived
from plasma or cells.
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26. a)Plasma-derived mediators:
i) Complement activation
•increases vascular permeability (C3a,C5a)
•activates chemotaxis (C5a)
•opsonization(C3b,C3bi)
ii) Factor XII (Hegmanfactor) activation
–Its activation results in recruitment of four systems:
•the kinin, clotting, fibrinolytic and the compliment systems.
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27. b) Cell-derived chemical mediators:
•Cell-derived chemical mediators include:
–Histamine
–Serotonine
–Lysosomal enzymes
–Prostaglandines
–Platelet activating factor
–Activated oxygen species
–Nitric oxide
–Cytokines
–Leukotrinesetc.
•Most mediators perform their biologic activities by initially binding
to specific receptors on target cells.
•Once activated and released from the cells, most of these mediators
are short lived.
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28. Chemical mediators of inflammation (EC: endothelial cells)
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29. Out come of Acute Inflammation
I)Resolution of tissue structure and function often
occurs if the injurious agent is eliminated.
II)Tissue destruction and persistent acute inflammation
III)Conversion to chronic inflammation
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30. Morphology of acute inflammation
1) Serous inflammation
•This is characterized by an outpouring of a thin fluid that is
derived from either the blood serum or secretion of
mesothelialcells lining the peritoneal, pleural, and
pericardial cavities.
•It resolves without reactions
2) Fibrinousinflammation
•More severe injuries result in greater vascular permeability
that ultimately leads to exudation of larger molecules such
as fibrinogens through the vascular barrier.
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31. •Fibrinous exudate is characteristic of inflammation in
serous body cavities such as the pericardium (butter and
bread appearance) and pleura.
•Course of fibrinous inflammation include:
–Resolution by fibrinolysis
–Scar formation between perietal and visceral surfaces i.e.
the exudates get organized
–Fibrous strand formation that bridges the pericardial
space.
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32. 3) Suppurative (Purulent) inflammation
This type of inflammation is characterized by the production
of a large amount of pus.
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33. •Pus is a thick creamy liquid, yellowish or blood stained in
colourand composed of
-A large number of living or dead leukocytes
-Necrotic tissue debris
-Living and dead bacteria
-Edema fluid
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34. Morphology of acute inflammation cont…
4) Catarrhal inflammation
•This is a mild and superficial inflammation of
the mucous membrane.
•It is commonly seen in the upper respiratory
tract following viral infections where mucous
secreting glands are present in large numbers,
eg. Rhinitis.
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35. 5) Pseudomembranous inflammation
•Extensive confluent necrosis of the surface
epithelium of an inflamed mucosa and severe acute
inflammation of the underlying tissues.
•The fibrinogens in the inflamed tissue coagulate
within the necrotic epithelium.
–E.g.; Dipthetricinfection of the pharynx or larynx and
Clostridium difficilleinfection in the large bowel
following certain antibiotic use.
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Morphology of acute inflammation cont…

36. Oral candidiasis: thrush Extensive cottage cheese like
plaques, colonies of Candida thatcan be removed by rubbing
with gauze (pseudomembranous)
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37. Course of acute inflammation
•Acute inflammation may end up in:
–Resolution
–Healing by fibrosis (scar formation).
–Abscess formation. However, if it is left untouched, it
may result in:
-Sinus formation -when an abscess cavity makes contact with
only one epithelial lining.
-Fistula formation: when an abscess tract connects two
epithelial surface.
-septicemia or Pyemia with subsequent metastatic abscess in
heart, kidney, brain etc
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38. CHRONIC INFLAMMATION
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39. CHRONIC INFLAMMATION
•Definition: Chronic inflammation can be defined as a
prolonged inflammatory process (weeks or months) where
an active inflammation, tissue destruction and attempts at
repair are proceeding simultaneously.
Causes of chronic inflammation:
1. Persistent infections
•Certain microorganisms associated with intracellular
infection such as tuberculosis, leprosy, certain fungi etc
characteristically cause chronic inflammation.
•These organisms are of low toxicity and evoke delayed
hypersensitivity reactions.
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40. 2. Prolonged exposure to nondegradable but partially
toxic substances either endogenous lipid components
which result in atherosclerosis or exogenous substances
such as silica, asbestos.
3. Progression from acute inflammation:
Acute inflammation almost always progresses to chronic
inflammation following:
•Persistent suppuration as a result of uncollapsedabscess cavities,
•foreign body materials (dirt, cloth, wool, etc),
•sequestrum in osteomyelitis,
•or a sinus/fistula from chronic abscesses.
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41. 4. Autoimmunity.
Autoimmune diseases such as rheumatoid arthritis and
systemic lupus erythematosisare chronic inflammations
from the outset.
Morphology:
Cells of chronic inflammation:
•Monocytes and Macrophages are the prima dona(primary
cells) in chronic inflammation.
•Macrophages arise from the common precursor cells in the
bone marrow, which give rise to blood monocytes.
•Macrophages are scavenger cells of the body.
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42. Other cells in chronic inflammation:
1. T-Lymphocytes are primarily involved in cellular immunity
with lymphokine production, and they are the key regulator
and effector cells of the immune system.
2. B-lymphocytes and Plasma cells produce antibody
directed either against persistent antigen in the
inflammatory site or against altered tissue components.
3. Mast cells and eosinophils appear predominantly in
response to parasitic infestations & allergic reactions.
•Neutrophilsare more common in acute inflammation.
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43. Classification of chronic inflammation:
•Chronic inflammation can be classified into the following
two types based on histologicfeatures:
1)Nonspecific chronic inflammation:
This involves a diffuse accumulation of macrophages and
lymphocytes at site of injury that is usually productive
with new fibrous tissue formations. E.g. Chronic
cholecystitis.
2) Specific inflammation (granulomatousinflammation):
is characterized by the presence of granuloma.
–A granuloma is a microscopic aggregate of epithelioid cells.
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44. Causes:
•Major causes of granulomatousinflammation include:
a) Bacterial: Tuberculosis, Leprosy, Syphilis, Cat scratch disease,
Yersiniosis
b) Fungal: Histoplasmosis, Cryptococcosis, Coccidioidomycosis,
Blastomycosis
c) Helminthic: Schistosomiasis
d) Protozoal: Leishmaniasis, Toxoplasmosis
e) Chlamydia: Lymphogranulomavenerum
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45. ❑SYSTEMIC EFFECTS OF INFLAMMATIONS
•The systemic effects of inflammation include:
a. Fever
b. Endocrine & metabolic responses
c. Autonomic responses
d. Behavioral responses
e. Leukocytosis
f. Leukopenia
g. Weight loss
a. Fever
•Fever is the most important systemic manifestation of inflammation.
•It is coordinated bythe hypothalamus & by cytokines (IL -1, IL-6,
TNF-α) released from macrophages and other cells.
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46. b. Endocrine and metabolic responses include:
•-The liver secrets acute phase proteins such as: C-reactive
proteins ,Complement and coagulation proteins.
c. Autonomic responses include:
-Redirection of blood flow from the cutaneous to the deep
vascular bed.
-Pulse rate and blood pressure (increased)
d. Behavioral responses include:
•-Rigor, chills, anoroxia, somnolence, and malaise.
e. Leucocytosis
-is also a common feature of inflammation, especially in
bacterial infections.
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47. -Most bacterial infections induce neutrophilia.
-Some viral infections such as infectious mononucleosis, &
mumps cause lymphocytosis.
-Parasitic infestations & allergic reactions such as bronchial
asthma & hay fever induce eosinophilia.
f. Leukopenia
-is also a feature of typhoid fever and some parasitic
infections.
g. Weight loss is thought to be due to the action of IL-1 and
TNF-α which increasecatabolism in skeletal muscle,
adipose tissue and the liver with resultant negative nitrogen
balance.
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